Nervelight - Intra-Operative Nerve Imaging Agent
Nervelight™, a topical, intraoperative nerve imaging agent that is selective for at-risk nerve tissue in cancer resections
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We have shown in vivo Proof-of-Concept of Nervelight™, a nerve imaging agent that is comprised of a commercially available Near InfraRed (NIR) dye in the 800 range attached to recombinant human Nerve Growth Factor (800-rhNGF). When Nervelight™ was applied topically, intra-operatively in an incision model of just-euthanized naïve rats, we showed selective uptake into cavernous nerves (below), facial nerves (below), and sciatic nerve (data not given). When studied recently in live animals, the selectivity and brightness of Nervelight™ is further enhanced. We will update this page when additional data is publicly available.
It is well established that rhNGF has a high affinity for tropomyosin kinase A (TrkA) receptors which are expressed on the distal ends of peripheral nerves. Our results confirm that the main mechanism underlying the selectivity of Nervelight™ is its binding to TrkA receptors that are exposed after incision. Of note: since rat neuroanatomy involving binding of NGF to TrkA is highly homologous in humans, these results are clinically predictive. In parallel, we have prototyped a “repurposed rhNGF” that we expect can be substituted for the research-grade material now currently used.
Intravitreal implants with FA-rhBDNF: optic neuritis, indirect Traumatic Optic Neuropathy (iTON)
Optic neuritis involves inflammation of the optic nerve, usually accompanied by pain in one eye. Although it may resolve without treatment, the Standard of Care is high-dose, systemic glucocorticoids. About half of cases presage multiple sclerosis in about two years. Separately, indirect Traumatic Optic Neuropathy (iTON) is a condition that affects our Troops, our Wounded Warriors and our Veterans, almost always after they have been exposed to blast or chemical trauma. Recently, the Rex lab at Vanderbilt University Medical Center (Bernardo-Colón et al., 2019) showed that inflammation of the optic nerve is one of the first pathologies to result from blast trauma. We have shown Proof-of-Concept of drug delivery of small molecules to the optic nerve. We attached a commercially available Near InfraRed (NIR) dye in the 800 region to recombinant human brain-derived neurotrophic factor (800-rhBDNF, Benlight™). In two studies, when injected intravitreally or intracisternally, 800-rhBDNF appeared to reach the optic nerve heads in the posterior of the eye, in the retinal layer that connects the optic nerve to the eye.
Study #1: intravitreal 800-rhBDNF
This was a 2X2 study in which we tested intravitreal (IVT) and topical 800-rhBDNF and IVT and topical 800-rhNGF (unpublished data).
Study #2: intracisternal 800-rhBDNF
This study showed that when 800-rhBDNF is injected intracisternally in a single dose, midline at the base of the skull where the optic nerve originates, the NIR dye was localized to the optic nerve and transported to the optic nerve heads. Data were presented in a poster in collaboration with Absorption Systems (San Diego, CA) at Military Health System Research Symposium, August 2019. An excerpt from that poster is given below.
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